Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens

Abstract

BackgroundDietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene’s molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans.MethodsIn this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected.ResultsWe observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues.ConclusionsTaken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders

“…Reduced nuclear factor-kappa B (NF-κB) expression, serum level of oxidative stress marker malondialdehyde (MDA) Improved nuclear factor erythroid 2 expressions Reduced the expression of signal transducer and activator of transcription 3 (STAT3) Induced the protein inhibitor of activated STAT3 expression [44,45] Induced cell cycle arrest and modified the potential of mitochondrial membrane, DNA fragmentation [46,47] Treatment of HGC-27 cells with lycopene exhibited significant improvement in LC3-I, Phosphorylated Extracellular Signal-Regulated Kinase (p-ERK) proteins expressions [48] Reduced NADPH oxidase (NOX) 4 activity Lowered invasion, migration, and adhesion, NOX activity, matrix metalloproteinase (MMP)-9, MMP-2 activities and NOX4 protein expression [49] Reduced…”

Protective Effect of Lycopene against Reperfusion Injury in Rats with Ovarian Torsion: A Biochemical and Histopathological Evaluation

“…19 Therefore, several studies have focused on pharmaceutical agents with antioxidant effects to prevent ovarian IR damage in animal models. 1,3,5,18 The ischemia that develops due to torsion has been reported to increase the blood levels of lipid peroxidation products. 20 It is known that antioxidant treatment helps prevent tissue damage related to increases in oxidant production.…”

“… 13 In oxidative stress, there is an imbalance between the production and elimination of ROS. 3 The IR condition oxidizes cellular membrane lipids and leads to the formation of toxic products such as MDA. 14 On the other hand, cellular protection against oxidative damage is provided by antioxidant enzymes and nonenzymatic compounds such as GSH or SOD.…”

“…1 Oxidative trauma occurs in a cell when the concentration of generated ROS exceeds that cell's antioxidant capability. 2,3 Various antioxidants have been used for the prevention of oxidative injury and inflammation in ovaries subject to IR injury. 4 Malondialdehyde (MDA) is the basic product of lipid peroxidation and is used to determine oxidative stress levels.…”

“…1 Lycopene, a type of carotenoid, has antioxidant and chemopreventive properties. 3 In our study, rats with ovarian torsion-detorsion damage were evaluated for the effects of lycopene. Moreover, the study evaluated the degree of ovarian tissue damage by histopathological examination and biochemically assessed the levels of MDA, GSH, myeloperoxidase (MPO), and superoxide dismutase (SOD) enzyme activity.…”